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Search Results: 1 - 10 of 162332 matches for " William H. Westra "
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Early glandular neoplasia of the lung
William H Westra
Respiratory Research , 2000, DOI: 10.1186/rr28
Abstract: Lung cancer is the leading cause of cancer death in the industrialized world [1]. A dismally low cure rate largely reflects the propensity of lung cancer to present as clinically advanced tumors: most lung cancers are discovered late during their clinical course, by which time the options for effective therapeutic intervention are limited. Of these lung cancers, adenocarcinoma is now the most common subtype [2]. This subtype is particularly notorious for eluding early detection. Even vigilant screening of sputum samples for morphologic evidence of early glandular neoplasia in individuals at risk is ineffective in curbing mortality rates [3]. Adenocarcinomas of the lung tend to arise peripherally, and malignant cells are not shed into the sputum until these tumors have developed into sizeable and frankly invasive cancers. The inability to detect early glandular neoplasia has not only frustrated efforts to treat patients effectively but has also hampered attempts to address fundamental questions about how normal alveolar cells become malignant. Understanding the early steps of lung tumorigenesis at the molecular genetic level might facilitate the development of more effective strategies for the prevention, early diagnosis, and treatment of lung cancer.Unlike central bronchogenic tumors, in which unwavering progression through the metaplasia-dysplasia-carcinoma in situ sequence has long been recognized, the morphologic progression of early glandular neoplasia has been shrouded in mystery. Earliest attempts to explain the origin of lung adenocarcinoma date back at least to the observation by Friedrich in 1939 that peripheral lung cancers often coincide with subpleural anthrocotic scars [4]. According to the 'scar cancer' concept, scar formation acts as an inciting focus for epithelial regeneration, proliferation, and ultimate neoplastic transformation. Over time, this concept has fallen into disrepute. Studies indicate that tumor-associated scarring, in most instances,
Following Mitochondrial Footprints through a Long Mucosal Path to Lung Cancer
Santanu Dasgupta, Rex C. Yung, William H. Westra, David A. Rini, Johann Brandes, David Sidransky
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006533
Abstract: Background Mitochondrial DNA (mtDNA) mutations are reported in different tumors. However, there is no information on the temporal development of the mtDNA mutations/content alteration and their extent in normal and abnormal mucosa continuously exposed to tobacco smoke in lung cancer patients. Methodology We examined the pattern of mtDNA alteration (mtDNA mutation and content index) in 25 airway mucosal biopsies, corresponding tumors and normal lymph nodes obtained from three patients with primary lung cancers. In addition, we examined the pattern of mtDNA mutation in corresponding tumors and normal lymph nodes obtained from eight other patients with primary lung cancers. The entire 16.5 kb mitochondrial genome was sequenced on Affymetrix Mitochip v2.0 sequencing platform in every sample. To examine mtDNA content index, we performed real-time PCR analysis. Principal Findings The airway mucosal biopsies obtained from three lung cancer patients were histopathologically negative but exhibited multiple clonal mtDNA mutations detectable in the corresponding tumors. One of the patients was operated twice for the removal of tumor from the right upper and left lower lobe respectively within a span of two years. Both of these tumors exhibited twenty identical mtDNA mutations. MtDNA content increased significantly (P<0.001) in the lung cancer and all the histologically negative mucosal biopsies except one compared to the control lymph node. Conclusions/Significance: Our results document the extent of massive clonal patches that develop in lifetime smokers and ultimately give rise to clinically significant cancers. These observations shed light on the extent of disease in the airway of smokers traceable through mtDNA mutation. MtDNA mutation could be a reliable tool for molecular assessment of respiratory epithelium exposed to continuous smoke as well as disease detection and monitoring. Functional analysis of the pathogenic mtDNA mutations may be useful to understand their role in lung tumorigenesis.
Suprabasin Is Hypomethylated and Associated with Metastasis in Salivary Adenoid Cystic Carcinoma
Chunbo Shao,Marietta Tan,Justin A. Bishop,Jia Liu,Weiliang Bai,Daria A. Gaykalova,Takenori Ogawa,Ami R. Vikani,Yuri Agrawal,Ryan J. Li,Myoung Sook Kim,William H. Westra,David Sidransky,Joseph A. Califano,Patrick K. Ha
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048582
Abstract: Salivary gland adenoid cystic carcinoma (ACC) is a rare cancer, accounting for only 1% of all head and neck malignancies. ACC is well known for perineural invasion and distant metastasis, but its underlying molecular mechanisms of carcinogenesis are still unclear.
Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors
Megan L. Durr,Wojciech K. Mydlarz,Chunbo Shao,Marianna L. Zahurak,Alice Y. Chuang,Mohammad O. Hoque,William H. Westra,Nanette J. Liegeois,Joseph A. Califano,David Sidransky,Patrick K. Ha
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010828
Abstract: Methylation profiling of tumor suppressor gene (TSGs) promoters is quickly becoming a powerful diagnostic tool for the early detection, prognosis, and even prediction of clinical response to treatment. Few studies address this in salivary gland tumors (SGTs); hence the promoter methylation profile of various TSGs was quantitatively assessed in primary SGT tissue to determine if tumor-specific alterations could be detected.
Glyphosate Resistance in Giant Ragweed (Ambrosia trifida L.) from Mississippi Is Partly Due to Reduced Translocation  [PDF]
Vijay K. Nandula, Alice A. Wright, Christopher R. Van Horn, William T. Molin, Phil Westra, Krishna N. Reddy
American Journal of Plant Sciences (AJPS) , 2015, DOI: 10.4236/ajps.2015.613211
Abstract: A giant ragweed population from a glyphosate-resistant (GR) soybean field in Mississippi, USA was suspected to be resistant to glyphosate. Greenhouse and laboratory studies were conducted to confirm and quantify the magnitude of glyphosate resistance in a resistant biotype selected from this population and to elucidate possible physiological and molecular mechanisms of glyphosate resistance. Glyphosate dose response studies indicated that ED50 (effective dose required to reduce plant growth by 50%) values for glyphosate-resistant (GR-MS) and glyphosate-susceptible (GS-MS) biotypes, based on percent injury, were 0.52 and 0.34 kg ae/ha glyphosate, respectively, indicating a 1.5-fold level of resistance in GR-MS. The absorption pattern of 14C-glyphosate in the two giant ragweed biotypes was similar throughout the measured time course of 168 h after treatment (HAT). The amount of 14C-glyphosate that translocated out of treated leaves of the GR-MS and GS-MS plants was similar up to 24 HAT. However, the GS-MS biotype translocated more (71% and 76% of absorbed at 48 and 96 HAT, respectively) 14C-glyphosate than the GR-MS biotype (44% and 66% of absorbed at 48 and 96 HAT, respectively) out of the treated leaf. No target site mutation was identified at the Pro106 location of the EPSPS gene of the GR-MS biotype. The mechanism of resistance to glyphosate in giant ragweed from Mississippi, at least, is due to reduced glyphosate translocation.
Respiratory Sensitization & Sickness from Welding/Burning Isocyanate Containing Paints  [PDF]
Terrence Stobbe, Ryan Westra
Journal of Geoscience and Environment Protection (GEP) , 2014, DOI: 10.4236/gep.2014.24007

The purpose of this paper is to make the environmental and occupational health community aware of a serious health risk associated with the common practice of burning industrial paint off of metal surfaces during or prior to welding. On four occasions bystanders and welder/burner personnel have experienced illness as a result of being exposed to the combustion products of isocyanate paints that were being burned off metal surfaces. In each case, the burning and the exposed people were outside in an open environment where the health risk was thought to be minimal due to the open environment with nominal wind movement through the work area. In one case, the person (a burner) developed permanent sensitization to phthalic anhydride as a result of the exposure. Phthalic anhydride was determined to be decomposition product of burned isocyanate paint. In the other three cases (which involved very short exposures), between two and six people became ill but did not develop sensitization. Their symptoms included dizziness, nausea, headache, and breathing difficulty the severity of which varied from very uncomfortable to temporarily incapacitating. This paper discusses the circumstances associated with each event, the approach used to determine that phthalic anhydride was a decomposition product, and some practical things that can be done to avoid having employees become victims of exposure.

Coordinated Activation of Candidate Proto-Oncogenes and Cancer Testes Antigens via Promoter Demethylation in Head and Neck Cancer and Lung Cancer
Ian M. Smith, Chad A. Glazer, Suhail K. Mithani, Michael F. Ochs, Wenyue Sun, Sheetal Bhan, Alexander Vostrov, Ziedulla Abdullaev, Victor Lobanenkov, Andrew Gray, Chunyan Liu, Steven S. Chang, Kimberly L. Ostrow, William H. Westra, Shahnaz Begum, Mousumi Dhara, Joseph Califano
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004961
Abstract: Background Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. Methodology/Principal Findings We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. Conclusions/Significance Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs in aerodigestive cancers, and BORIS is implicated in the coordinated promoter demethylation and reactivation of epigenetically silenced genes in human cancers.
Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Daria A. Gaykalova, Elizabeth Mambo, Ashish Choudhary, Jeffery Houghton, Kalyan Buddavarapu, Tiffany Sanford, Will Darden, Alex Adai, Andrew Hadd, Gary Latham, Ludmila V. Danilova, Justin Bishop, Ryan J. Li, William H. Westra, Patrick Hennessey, Wayne M. Koch, Michael F. Ochs, Joseph A. Califano, Wenyue Sun
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093102
Abstract: Development of head and neck squamous cell carcinoma (HNSCC) is characterized by accumulation of mutations in several oncogenes and tumor suppressor genes. We have formerly described the mutation pattern of HNSCC and described NOTCH signaling pathway alterations. Given the complexity of the HNSCC, here we extend the previous study to understand the overall HNSCC mutation context and to discover additional genetic alterations. We performed high depth targeted exon sequencing of 51 highly actionable cancer-related genes with a high frequency of mutation across many cancer types, including head and neck. DNA from primary tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected genes. These genes were mutated in 17 out of 37 (46%) studied HNSCC patients. Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients harbored 4-fold more TP53 mutations than HPV positive patients. These data confirm prior reports of the HNSCC mutational profile. Additionally, we detected mutations in two new genes, CEBPA and FES, which have not been previously reported in HNSCC. These data extend the spectrum of HNSCC mutations and define novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC without HPV infection.
A Process Model of Quantum Mechanics  [PDF]
William H. Sulis
Journal of Modern Physics (JMP) , 2014, DOI: 10.4236/jmp.2014.516176
Abstract: A process model of quantum mechanics utilizes a combinatorial game to generate a discrete and finite causal space, which can be defined as a self-consistent quantum mechanics. An emergent space-time  and continuous wave function arise through a non-uniform interpolation process. Standard non-relativistic quantum mechanics emerges under the limit of infinite information (the causal space grows to infinity) and infinitesimal scale (the separation between points goes to zero). This model has the potential to address several paradoxes in quantum mechanics while remaining computationally powerful.
De kolonale staten Suriname
P. Westra
Nieuwe West-Indische Gids , 1919,
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